SI2807183T1 - Synthetic appel mimetics for the treatment of cardiac insufficiency - Google Patents
Synthetic appel mimetics for the treatment of cardiac insufficiency Download PDFInfo
- Publication number
- SI2807183T1 SI2807183T1 SI201330999T SI201330999T SI2807183T1 SI 2807183 T1 SI2807183 T1 SI 2807183T1 SI 201330999 T SI201330999 T SI 201330999T SI 201330999 T SI201330999 T SI 201330999T SI 2807183 T1 SI2807183 T1 SI 2807183T1
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- Slovenia
- Prior art keywords
- nle
- polypeptide
- rprlc
- hkgp
- salt
- Prior art date
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- 206010019280 Heart failures Diseases 0.000 title claims 4
- 102000018746 Apelin Human genes 0.000 title claims 2
- 108010052412 Apelin Proteins 0.000 title claims 2
- BWVPHIKGXQBZPV-QKFDDRBGSA-N apelin Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCSC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)CCC1 BWVPHIKGXQBZPV-QKFDDRBGSA-N 0.000 title claims 2
- 229920001184 polypeptide Polymers 0.000 claims abstract 35
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 35
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 35
- 150000003839 salts Chemical class 0.000 claims abstract 14
- 150000001408 amides Chemical class 0.000 claims abstract 13
- 150000002148 esters Chemical class 0.000 claims abstract 13
- 206010007556 Cardiac failure acute Diseases 0.000 claims abstract 3
- 208000008589 Obesity Diseases 0.000 claims abstract 3
- 235000020824 obesity Nutrition 0.000 claims abstract 3
- 108091008803 APLNR Proteins 0.000 claims abstract 2
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract 2
- 206010003658 Atrial Fibrillation Diseases 0.000 claims abstract 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims abstract 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract 2
- 206010016807 Fluid retention Diseases 0.000 claims abstract 2
- 206010020772 Hypertension Diseases 0.000 claims abstract 2
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims abstract 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims abstract 2
- 208000006011 Stroke Diseases 0.000 claims abstract 2
- 206010042496 Sunburn Diseases 0.000 claims abstract 2
- 208000032109 Transient ischaemic attack Diseases 0.000 claims abstract 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract 2
- 208000027418 Wounds and injury Diseases 0.000 claims abstract 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract 2
- 206010003119 arrhythmia Diseases 0.000 claims abstract 2
- 230000006793 arrhythmia Effects 0.000 claims abstract 2
- 230000009787 cardiac fibrosis Effects 0.000 claims abstract 2
- 230000006378 damage Effects 0.000 claims abstract 2
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract 2
- 208000004104 gestational diabetes Diseases 0.000 claims abstract 2
- 208000014674 injury Diseases 0.000 claims abstract 2
- 230000000302 ischemic effect Effects 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 201000011461 pre-eclampsia Diseases 0.000 claims abstract 2
- 230000002265 prevention Effects 0.000 claims abstract 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims abstract 2
- 208000037803 restenosis Diseases 0.000 claims abstract 2
- 201000010875 transient cerebral ischemia Diseases 0.000 claims abstract 2
- 230000009529 traumatic brain injury Effects 0.000 claims abstract 2
- 206010047302 ventricular tachycardia Diseases 0.000 claims abstract 2
- 235000001014 amino acid Nutrition 0.000 claims 6
- -1 glycine amino acids Chemical class 0.000 claims 5
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 claims 2
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 2
- 239000000480 calcium channel blocker Substances 0.000 claims 2
- 235000018417 cysteine Nutrition 0.000 claims 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 125000001431 2-aminoisobutyric acid group Chemical group [#6]C([#6])(N*)C(*)=O 0.000 claims 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical group OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims 1
- 239000005541 ACE inhibitor Substances 0.000 claims 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims 1
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 claims 1
- FFFHZYDWPBMWHY-GSVOUGTGSA-N D-Homocysteine Chemical compound OC(=O)[C@H](N)CCS FFFHZYDWPBMWHY-GSVOUGTGSA-N 0.000 claims 1
- 102000002045 Endothelin Human genes 0.000 claims 1
- 108050009340 Endothelin Proteins 0.000 claims 1
- 102000010180 Endothelin receptor Human genes 0.000 claims 1
- 108050001739 Endothelin receptor Proteins 0.000 claims 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- FFFHZYDWPBMWHY-UHFFFAOYSA-N L-Homocysteine Natural products OC(=O)C(N)CCS FFFHZYDWPBMWHY-UHFFFAOYSA-N 0.000 claims 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims 1
- 108090000854 Oxidoreductases Proteins 0.000 claims 1
- 102000003743 Relaxin Human genes 0.000 claims 1
- 108090000103 Relaxin Proteins 0.000 claims 1
- 159000000021 acetate salts Chemical class 0.000 claims 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 230000008484 agonism Effects 0.000 claims 1
- FUOOLUPWFVMBKG-UHFFFAOYSA-N alpha-amino-isobutyric acid Natural products CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 239000003472 antidiabetic agent Substances 0.000 claims 1
- 229940125708 antidiabetic agent Drugs 0.000 claims 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 229940030606 diuretics Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims 1
- 239000002461 renin inhibitor Substances 0.000 claims 1
- 229940086526 renin-inhibitors Drugs 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 206010059027 Brugada syndrome Diseases 0.000 abstract 1
- 206010007558 Cardiac failure chronic Diseases 0.000 abstract 1
- 239000013543 active substance Substances 0.000 abstract 1
- 239000000556 agonist Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
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- A61M16/08—Bellows; Connecting tubes ; Water traps; Patient circuits
- A61M16/0816—Joints or connectors
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- A—HUMAN NECESSITIES
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/60—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation occurring through the 4-amino group of 2,4-diamino-butanoic acid
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
- A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
- A61M2016/0027—Accessories therefor, e.g. sensors, vibrators, negative pressure pressure meter
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
- A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
- A61M2016/003—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/35—Communication
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- A—HUMAN NECESSITIES
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- A61M2205/00—General characteristics of the apparatus
- A61M2205/50—General characteristics of the apparatus with microprocessors or computers
- A61M2205/502—User interfaces, e.g. screens or keyboards
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Anesthesiology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Child & Adolescent Psychology (AREA)
- Toxicology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261591557P | 2012-01-27 | 2012-01-27 | |
| US201261717760P | 2012-10-24 | 2012-10-24 | |
| US201261731697P | 2012-11-30 | 2012-11-30 | |
| EP13711953.3A EP2807183B1 (en) | 2012-01-27 | 2013-01-25 | Synthetic apelin mimetics for the treatment of heart failure |
| PCT/IB2013/050666 WO2013111110A2 (en) | 2012-01-27 | 2013-01-25 | Synthetic apelin mimetics for the treatment of heart failure |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI2807183T1 true SI2807183T1 (en) | 2018-05-31 |
Family
ID=47997598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201330999T SI2807183T1 (en) | 2012-01-27 | 2013-01-25 | Synthetic appel mimetics for the treatment of cardiac insufficiency |
Country Status (42)
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8673848B2 (en) * | 2012-01-27 | 2014-03-18 | Novartis Ag | Synthetic apelin mimetics for the treatment of heart failure |
| US8921307B2 (en) * | 2012-11-20 | 2014-12-30 | Novartis Ag | Synthetic linear apelin mimetics for the treatment of heart failure |
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